Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000530941 | SCV000652005 | uncertain significance | Atrioventricular septal defect 4 | 2022-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 88 of the GATA4 protein (p.Gly88Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 472776). This variant has not been reported in the literature in individuals affected with GATA4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.04%). |
Fulgent Genetics, |
RCV000765985 | SCV000897416 | uncertain significance | Atrial septal defect 2; Tetralogy of Fallot; Ventricular septal defect 1; Atrioventricular septal defect 4; Testicular anomalies with or without congenital heart disease | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001571509 | SCV001795998 | uncertain significance | not provided | 2020-11-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 472776; Landrum et al., 2016) Observed in 4/25666 (0.016%) alleles in large population cohorts (Lek et al., 2016) At the protein level, in silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function At the mRNA level, in silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |